Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm
Authors: Jane E. Brumbaugh, Edward F. Bell, Barbara T. Do, Rachel G. Greenberg, Barbara J. Stoll, Sara B. DeMauro, Heidi M. Harmon, Susan R. Hintz, Abhik Das, Karen M. Puopolo, Namasivayam Ambalavanan, Kirstin J. Bailey, Fred J. Biasini, Waldemar A. Carlo, Stephanie A. Chopko, Monica V. Collins, Shirley S. Cosby, Kristen C. Johnston, Mary Beth Moses, Kathleen G. Nelson, Cryshelle S. Patterson, Myriam Peralta-Carcelen, Vivien A. Phillips, Julie Preskitt, Richard V. Rector, Sally Whitley, Barbara Alksninis, Carmena Bishop, Robert T. Burke, Melinda Caskey, Angelita M. Hensman, Laurie Hoffman, Katharine Johnson, Martin Keszler, Mary Lenore Keszler, Andrea M. Knoll, Vita Lamberson, Abbot R. Laptook, Theresa M. Leach, Emilee Little, Elizabeth C. McGowan, William Oh, Lucille St. Pierre, Bonnie E. Stephens, Suzy Ventura, Elisa Vieira, Betty R. Vohr, Victoria E. Watson, Kelly R. Coleman, Stephanie Guilford, Michelle E. Hartley-McAndrew, Satyan Lakshminrusimha, Emily Li, Anne Marie Reynolds, Michael G. Sacilowski, Ashley Williams, William A. Zorn, Monika Bhola, Avroy A. Fanaroff, Harriet G. Friedman, Anna Maria Hibbs, Nancy S. Newman, Allison H. Payne, Bonnie S. Siner, Michele C. Walsh, Deanne E. Wilson-Costello, Gulgun Yalcinkaya, Michael S. Caplan, Barbara Alexander, Traci Beiersdorfer, Kate Bridges, Tanya E. Cahill, Edward F. Donovan, Juanita Dudley, Estelle E. Fischer, Teresa L. Gratton, Cathy Grisby, Devan Hayes, Jody Hessling, Lenora Denise Jackson, Alan H. Jobe, Suhas G. Kallapur, Kristin Kirker, Stephanie L. Merhar, Holly L. Mincey, Greg Muthig, Brenda B. Poindexter, Kurt Schibler, Sara Stacey, Jean J. Steichen, Stacey Tepe, Julia Thompson, Marcia Worley Mersmann, Sandra Wuertz, Kimberly Yolton, Richard A. Polin, Sally S. Adams, Luc P. Brion, Lijun Chen, Maria M. De Leon, Frances Eubanks, Alicia Guzman, Gaynelle Hensley, Elizabeth T. Heyne, Roy J. Heyne, Jackie F. Hickman, Lizette E. Lee, Melissa H. Leps, Linda A. Madden, E. Rebecca McDougald, Nancy A. Miller, Janet S. Morgan, Lara Pavageau, Charles R. Rosenfeld, Walid A. Salhab, Pablo J. Sánchez, Pollieanna Sepulveda, Catherine Twell Boatman, Diana M. Vasil, Jillian Waterbury, Myra H. Wyckoff, Patricia L. Ashley, Kathy J. Auten, C. Michael Cotten, Joanne Finkle, Kimberley A. Fisher, Ronald N. Goldberg, Ricki F. Goldstein, Sandra Grimes, Kathryn E. Gustafson, Melody B. Lohmeyer, William F. Malcolm, Ira Adams-Chapman, Ann Blackwelder, Diane I. Bottcher, David P. Carlton, Sheena L. Carter, Ellen C. Hale, Salathiel Kendrick-Allwood, Judith Laursen, Yvonne C. Loggins, Colleen Mackie, Maureen Mulligan LaRossa, Ravi M. Patel, Amy Sanders, Irma Seabrook, Gloria V. Smikle, Lynn Wineski, Esther G. Akpa, Nora I. Alaniz, Elizabeth Allain, Julie Arldt-McAlister, Pamela J. Bradt, Katrina Burson, Allison G. Dempsey, Susan E. Dieterich, Andrea F. Duncan, Elizabeth Eason, Patricia W. Evans, Beverly Foley Harris, Claudia I. Franco, Carmen Garcia, Charles E. Green, Donna J. Hall, Margarita Jimenez, Janice John, Patrick M. Jones, Kathleen A. Kennedy, Amir M. Khan, Saba Khan Siddiki, Layne Lillie, Anna E. Lis, Terri L. Major-Kincade, Karen Martin, Sara C. Martin, Georgia Elaine McDavid, Shannon L. McKee, Brenda H. Morris, Patricia Ann Orekoya, Claudia Pedrozza, Carrie M. Perez, Patti L. Pierce Tate, Stacey Reddoch, Shawna Rodgers, Maegan C. Simmons, Daniel K. Sperry, Emily K. Stephens, Jon E. Tyson, Laura L. Whitely, Sharon L. Wright, Anna M. Dusick, Susan Gunn, Faithe Hamer, Dianne E. Herron, Abbey C. Hines, Jeffery Joyce, James A. Lemons, Carolyn Lytle, Lucy C. Miller, Heike M. Minnich, Lu-Ann Papile, Leslie Richard, Lucy C. Smiley, Gregory M. Sokol, Leslie Dawn Wilson, Michael J. Acarregui, Tarah T. Colaizy, John M. Dagle, Diane L. Eastman, Claire A. Goeke, Karen J. Johnson, Jonathan M. Klein, Nancy J. Krutzfield, Mendi L. Schmelzel, Jacky R. Walker, John A. Widness, Donia B. Bass, Dan L. Ellsbury, Tracy L. Tud, Charles R. Bauer, Maria Calejo, Shahnaz Duara, Ruth Everett-Thomas, Sylvia Fajardo-Hiriart, Silvia M. Frade Eguaras, Andrea Garcia, Michelle Harwood Berkovits, Helina Pierre, Arielle Riguard, Alexandra Stoerger, Lisa Gaetano, Cheri Gauldin, Anne M. Holmes, Kathy Johnson, Howard W. Kilbride, Eugenia K. Pallotto, Prabhu S. Parimi, Allison Scott, William E. Truog, Gail E. Besner, Erna Clark, Christine A. Fortney, Julie Gutentag, Sudarshan R. Jadcherla, Patricia Luzader, Nathalie L. Maitre, Leif D. Nelin, Nehal A. Parikh, Courtney Park, Julie C. Shadd, Melanie Stein, Margaret Sullivan, Andrew A. Bremer, Rosemary D. Higgins, Stephanie Wilson Archer, Soraya Abbasi, Judy C. Bernbaum, Christine Catts, Aasma S. Chaudhary, Noah Cook, Dara M. Cucinotta, Eric C. Eichenwald, Marsha Gerdes, Sarvin Ghavam, Hallam Hurt, Haresh Kirpalani, Toni Mancini, Barbara Schmidt, Jonathan M. Snyder, Sarith Vangala, Kristina Ziolkowski, Julie Babish Johnson, Kyle Binion, Melissa Bowman, Erica Burnell, Carl T. D'Angio, Caitlin Fallone, Osman Farooq, Ronnie Guillet, Cassandra A. Horihan, Julianne Hunn, Diane Hust, Rosemary L. Jensen, Rachel Jones, Jennifer Kachelmeyer, Alison Kent, Emily Kushner, Deanna Maffett, Kimberly G. McKee, Joan Merzbach, Gary J. Myers, Constance Orme, Dale L. Phelps, Diane M. Prinzing, Linda J. Reubens, Daisy Rochez, Mary Rowan, Premini Sabaratnam, Ann Marie Scorsone, Holly I.M. Wadkins, Kelley Yost, Lauren Zwetsch, Carla M. Bann, Margaret M. Crawford, Jenna Gabrio, Marie G. Gantz, Betty K. Hastings, David Leblond, Jamie E. Newman, Jeanette O’Donnell Auman, Carolyn M. Petrie Huitema, W. Kenneth Poole, Dennis Wallace, Kristin M. Zaterka-Baxter, Michelle L. Baack, Megan Broadbent, Chelsey Elenkiwich, Megan M. Henning, Laurie A. Hogden, Marian M. Adams, Dona Bahmani, M. Bethany Ball, Barbara Bentley, Elizabeth F. Bruno, Valerie Y. Chock, Alexis S. Davis, Maria Elena DeAnda, Anne M. DeBattista, Beth A. Earhart, Lynne C. Huffman, Magdy Ismael, Jean G. Kohn, Casey E. Krueger, Julie C. Lee-Ancajas, Janice Lowe, Ryan E. Lucash, Andrew W. Palmquist, Jessica Patel, Melinda S. Proud, Elizabeth N. Reichert, Dharshi Sivakumar, Nicholas H. St. John, David K. Stevenson, Heather L. Taylor, Krisa P. Van Meurs, Natalie Wager, R. Jordan Williams, Hali Weiss, Ana K. Brussa, Paige T. Church, John M. Fiascone, Ivan D. Frantz, Anne Furey, Anne Kurfiss, Brenda L. MacKinnon, Elisabeth C. McGowan, Ellen Nylen, Cecelia E. Sibley, Teresa Chanlaw, Uday Devaskar, Meena Garg, Rachel Geller, Isabell B. Purdy, Kathy Arnell, Clarence Demetrio, Neil N. Finer, Martha G. Fuller, Christopher Henderson, David Kaegi, Maynard R. Rasmussen, Wade Rich, Yvonne E. Vaucher, Paul R. Wozniak, Janice Bernhardt, Carl L. Bose, Gennie Bose, Cynthia L. Clark, Matthew Maxwell Laughon, Diane D. Warner, Janice Kay Wereszczak, Conra Backstrom Lacy, Tara Dupont, Janell Fuller, Mary Hanson, Carol H. Hartenberger, Elizabeth Kuan, Jean R. Lowe, Robin K. Ohls, Sandra Sundquist Beauman, Rebecca A. Thomson, Kristi L. Watterberg, John Barks, Martha D. Carlson, Mary K. Christensen, Stephanie A. Wiggins, Subrata Sarkar, Shawna Baker, Mariana Baserga, Karie Bird, Jill Burnett, Susan Christensen, Laura Cole Bledsoe, Sean D. Cunningham, Brandy Davis, Jennifer O. Elmont, Roger G. Faix, Becky Hall, Erika R. Jensen, Jennifer J. Jensen, Jamie Jordan, Manndi C. Loertscher, Trisha Marchant, Earl Maxson, Kandace M. McGrath, Stephen D. Minton, Galina Morshedzadeh, Karen A. Osborne, D. Melody Parry, Carrie A. Rau, Brixen A. Reich, Susan T. Schaefer, Mark J. Sheffield, Cynthia Spencer, Michael Steffen, Kelly Stout, Ashley L. Stuart, Katherine Tice, Kimberlee Weaver-Lewis, Sarah Winter, Kathryn D. Woodbury, Bradley A. Yoder, Karen Zanetti, Korinne Chiu, Robert G. Dillard, Deborah Evans Allred, Donald  J. Goldstein, Raquel Halfond, Barbara G. Jackson, T. Michael O’Shea, Nancy J. Peters, Carroll Peterson, Ellen L. Waldrep, Lisa K. Washburn, Cherrie D. Welch, Melissa Whalen Morris, Gail Wiley Hounshell, Stephen D. Kicklighter, Ginger Rhodes-Ryan, Donna White, Katherine Abramczyk, Prashant Agarwal, Monika Bajaj, Rebecca Bara, Elizabeth Billian, Sanjay Chawla, Kirsten Childs, Lilia C. De Jesus, Debra Driscoll, Melissa February, Laura A. Goldston, Mary E. Johnson, Geraldine Muran, Girija Natarajan, Bogdan Panaitescu, Athina Pappas, Jeannette E. Prentice, Seetha Shankaran, Beena G. Sood, Diane F. White, Eunice Woldt, Christine G. Butler, Patricia Cervone, Richard A. Ehrenkranz, Patricia Gettner, Sheila Greisman, Harris C. Jacobs, Monica Konstantino, JoAnn Poulsen, Elaine Romano, Janet Taft, Joanne Williams
Journal: JAMA Network Open (2022)

Importance Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm. Objective To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age. Design, Setting, and Participants This cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks’ gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers. Exposures Culture-confirmed LOM. Main Outcomes and Measures Incidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021). Results Among 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 ( P &amp;amp;lt; .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 ( P &amp;amp;lt; .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P &amp;amp;lt; .001) and among those with culture-confirmed LOS (23%-79%, P &amp;amp;lt; .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus , 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection. Conclusions and Relevance In this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.